1. Age at First Measles-Mumps-Rubella Vaccination in Children with Autism and School-matched Controls: A Population-Based Study in Metropolitan Atlanta
F. DeStefano, MD, MPH 2, T. Karapurkar, MPH3, W. W. Thompson, PhD2, M. Yeargin-Allsopp, MD1, C. Boyle, PhD1
1 National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention
2 National Immunization Program, Centers for Disease Control and Prevention
3 Battelle Centers for Public Health Research and Evaluation
Background
Classification of Autism Subgroups
Results: Age at First MMR Vaccination and Autism by Demographic Factors
Subgroup 1: Children without any indication of developmental delay or pre-existing condition (PEC) prior to age 12 months
Subgroup 2: Children with any indication of loss of age-appropriate developmental skills (regression) or appropriate skills that failed to progress
Subgroup 3: Children with and without coexisting mental retardation (MR)
Recent estimates of autism prevalence are as high as 2-6 per 1,000.
There is growing concern over the apparent rise in prevalence of autism.
The causes are largely unknown
Evidence for strong genetic component
Environmental factors, such as vaccines, have been implicated
Case Subgroup
Cases
(N)
< 18 mo
OR (95% CI)
< 24 mo
< 36 mo
All Cases
624
1.12 ( )
1.21 ( )
1.49 ( )
Males
500
1.22 ( )
1.29 ( )
1.67 ( )
Females
124
0.83 ( )
0.96 ( )
1.06 ( )
3-5 yrs
214
1.08 ( )
1.66 ( )
2.34 ( )
6-10 yrs
410
1.14 ( )
1.10 ( )
1.33 (
Data Collection
Measles-Mumps-Rubella (MMR) Vaccine and Autism
Two main arguments in support of association
Prevalence of autism has been increasing at the same time that childhood
vaccination coverage has increased
Temporal associations in which autistic characteristics become more
apparent around the time of MMR vaccination.
Georgia Standard Immunization Form
Vaccinations required by law for entry into early intervention and school programs
- MMR, DTP, OPV/IPV, Hepatitis B (in 1992)
Vaccine exemption data were also collected if available.
In birth certificate subsample (N=311), most OR’s were lower and all CI’s included 1.0.
(data not shown)
More case (93.4 %) than control children (90.6) were vaccinated before 36 months.
- Association strongest among 3-5 year old children in both total and birth certificate
samples.
Child’s Birth Certificate
Child’s sex, child’s birth date, mother’s race, multiple gestation, birth weight, and
maternal age and education
MADDSP
Other developmental disabilities, and co-existing medical conditions
Institute of Medicine (IOM) Statement, 2001
IOM reviewed MMR-autism hypothesis and rejected causal association based
on findings of previous epidemiologic investigations.
Encouraged additional studies to evaluate the possibility that subgroups of
children might be at increased risk of autism from MMR vaccination
Results: Age at First MMR Vaccination and Autism, by Clinical Subgroups
Analytic Approach
Study Purpose
Compared distribution of ages at first MMR vaccination by case status
Overall distributions of age at vaccination
By three age cut-offs:
< 18 months of age – an indicator of ‘on time’ vaccination
< 24 months of age – the age by which atypical development has become apparent
< 36 months of age – the age requirement to meet DSM-IV criteria for autism
Conditional Logistic Regression Models
Likelihood ratio test for examining overall distributions of ages at first MMR vaccination
Odds ratios (ORs) calculated for the association between autism and age at MMR
vaccination dichotomized according to three age cut-offs (18 mo, 24 mo & 36 mo).
Total sample- unadjusted analyses
Birth certificate sample – ORs adjusted for birth certificate factors (birth weight,
multiple gestation, maternal age and education)
Study purpose: To compare ages at first MMR vaccination between children with autism and children without autism in the total population and in select subgroups, including children with regression in development
Case Subgroup
< 18 mo
OR (95% CI)
< 24 mo
OR(95% CI)
< 36 mo
No PEC or delay < 1 year (N=390)
1.07 ( )
1.14 ( )
1.51 ( )
Regression or Plateau (N=80)
1.37 ( )
1.30 ( )
1.45 ( )
With MR (N=376)
1.06 ( )
1.09( )
1.21( )
Without MR (N=248)
1.23( )
1.46( )
2.45( )
Study Design and Population
Case-control study design
Cases: 624 children with ASD
Identified through MADDSP Autism Surveillance in 1996
Controls:1,824 children selected from schools
3:1 controls: cases matched on age, gender, and school of attendance
In birth certificate subsample (N=311), ORs were lower or similar to those in total sample
and all CI’s included 1.0 (data not shown).
Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP)
Results: Age at First MMR Vaccination by Case Status for Total Sample
Summary
Similar proportion of case and control children vaccinated around recommended age
for MMR vaccination (< 18 months) and before the age at which atypical development
becomes apparent (24 months).
No significant associations found for either age cut-offs < 18 or < 24 months among all
cases and in case subgroups
Vaccination < 36 months more common in case children than control children, ,particularly
in 3-5 year old age group
- Possibly reflecting immunization requirements of early intervention programs.
Population based program begun in 1991: 3-10 year old children in the 5 counties of
Metropolitan Atlanta
Multiple source ascertainment of select developmental disabilities
MADDSP Autism Surveillance
Case definition based on DSM IV criteria:
Autistic Disorders:
Atypical Autism (PDD-NOS & Asperger’s Syndrome):
Case status:
Established by a team of expert reviewers
MADDSP Study Areas
Most case (70.5 %) and control
(67.5%) children were vaccinated
between months.
Distributions not significantly different
(p=0.22)